Natural and artificial oligonucleotides are capable of assuming many differ
ent conformations and functions. Here we present results of an NMR restrain
ed molecular modelling study on the conformational preferences of the modif
ied decanucleotide d((m)C1G2(m)C3G4C5(L)G6(L)(m)C7G8(m)C9G10).d((m)C11G12(m
)C13G14C15(L)G(L)16(m)C17G18(m)C19G20) which contains L deoxynucleotides in
its centre, This chimeric DNA was expected to form a right-left-right-hand
ed B-type double-helix (BB*B) at low salt concentration. Actually, it matur
ed into a fully right-handed double helix with its central C(L)pG(L) core f
orming a right-handed Z-DNA helix embedded in a B-DNA matrix (BZ*B), The in
terplay between base-base and base-sugar stackings within the core and its
immediately adjacent residues was found to be critical in ensuring the stab
ilisation of the right-handed helix, The structure could serve as a model f
or the design of antisense oligonucleotides resistant to nucleases and capa
ble of hybridising to natural DNAs and RNAs.